CN1623534A - 肌酸的新用途 - Google Patents
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A61P11/08—Bronchodilators
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
本发明描述了肌酸在制备治疗心脏和/或呼吸功能不全药物方面的新用途。
Description
本申请是申请号为97199783.7、申请日为1997年11月10日、发明名称为“肌酸的新用途”的中国专利申请的分案申请。
技术领域
本发明涉及肌酸的一种新用途，特别是在制备治疗心脏和/或呼吸功能不全的药物方面的新用途。
背景技术
肌酸是一种在人和动物的能量代谢中起重要作用的物质。人体能够自发产生一定量的这种生命必需的化合物，而不定量的肌酸却是经由日常饮食，基本上是经由肉食引入的(J.B.Walker等，《酶学进展(Adv.Enzymol.)》.1979，50，177-242)。
众所周知，外源性肌酸能够增进正常人和运动员的瞬时和剧烈运动(最大运动量)的能力(P.L.Greenhaff，《临床科学(Clinical Science)》(1993)，84，565-571；P.D.Balsom等，《斯堪的纳维亚运动医学与科学(Scand.J.Med.Sci.Sports)》，1993，3：143-149)。
使用较大剂量的肌酸(15-20g/天)也已经获得了实现最大运动量的效果。
但是，这种剂量会引起相当大的副作用诸如肠胃功能失调、体重增加，水潴留，这是长期使用肌酸的缺点，因而不宜服用肌酸来增进持续(持久)运动的能力(P.D.Balsom等，《斯堪的纳维亚生理学报(Acta Physiol.Scand)》1993，149，521-523)。
另外，上述这种为实现最大运动量所需的剂量应该再分成几个“日剂量”，已知一次给药超过所谓“肾阈值”，多于4-5g的剂量及任何过量物质就会在没有实现任何全身性有效功能的情况下直接经尿排出。
肌酸的口服给药已在心脏功能不全患者中进行过研究，结果证明此药能显著增进最大运动量。
但是，在这类病例中要服用很大剂量(15g/日)才能得到药效(A.Gordon等，《心脏血管研究(Cardiovascular Research)》30(1995)413-418)。
由于上述原因，这种剂量除非严密控制而且短期内实现的临床试验之外是不能应用的。
显然，前面提到的对正常人明显的那些副作用势必给那些心血管系统因病受损和/或疲劳的患者带来极高的风险，因而这是肌酸给药的一个真正障碍。
另外，与健康人相比，心脏和/或呼吸紊乱患者的肌肉能量代谢进一步受损(B.M.Massie等，《循环系(Circulation)》vol.78，NO.2，1988，320-326；B.M.Massie等，《美国心脏病学杂志(The AmericanJournal of Cardiology)》1987，60，309-315)，因而在治疗时不仅要考虑因基础病理学早已危急的一般情况，还要权衡能量有效利用率降低的负面作用。
尽管对健康人的实验结果证明，10-15g/日以下的肌酸剂量是不灵验的，更小的剂量(1-4g/日)却已经用作一种有明显抗虚弱作用的食品添加剂添加在老年人、体弱者和/或素食者的饮食中。
再者，这种剂量已经有了更好的长期耐药性。
发明内容
意想不到的是，现已发现小剂量(1-4g/日)的肌酸给药使肌肉的能量代谢效率能够提高，并能使心脏和/或呼吸功能不全患者的运动能力得到全面增进。
因此，本发明的目的是肌酸在制备治疗心脏和/或呼吸功能不全药物方面的用途，其中肌酸的剂量为1-4g/日。
特别是，业已意想不到地发现；按上述剂量应用肌酸，特别有利于制备治疗晚期阻塞性支气管病的药物。
按照本发明所述的方法使用常规的制药技术能够实现该药物的制备，该药物可以包含，除赋形剂和/或药物可接受的稀释剂之外，还有一种或多种活性组分，例如氨基酸如精氨酸、缬氨酸、亮氨酸和异亮氨酸、复合糖和/或抗氧化剂。
具体实施方式
下列实施例是具体说明本发明的，但不会以任何方式对本发明进行限制。
实施例
七位晚期阻塞性支气管病患者(5男2女，平均年龄67岁)在基础水平状况下做了“步行试验”。试验是沿一平坦表面步行6分钟。为了安全也因需要实时收集数据，在试验期间使心率和静脉血中氧的去饱和作用保持在恒定控制之下。
6分钟后，把各位患者走过的距离，终点心率和氧的去饱和作用记录下来。
每一试验的终结，用一种专门的12分制标度(叫做Borg标度)对各位患者察觉的“呼吸困难”进行评定。
然后每隔一定时间给各位患者服用一种含1g肌酸的药物，每日三次；经过10天治疗之后，让患者再一次做“步行试验”。
治疗后的全部患者所走过的距离都有明显的增加。
健康状况的这一好转，平均来说约为32％，与基础水平相比是很明显的(图1显示，以直方图形式，七位患者走过的距离和相对平均值：p＝0.01)也符合用学生的T-试验对成对数据进行的统计分析。
因此证明，小剂量的肌酸给药能够增进持续运动的耐力。
而且还意想不到地发现，全部患者都以低于肌酸治疗前测得的心率数据填满了运动原始记录，唯一的例外是有一位患者不在心率分析范围之内，他在起点试验中只能走2分钟，终点试验中走3分钟。心率的平均降低量为12搏动/分钟左右。在用学生的T-试验的统计分析中也是有显著差异的(见图2显示，以直方图形式，七位患者的心率及相对平均值)。
患者们的主观反应也证实心血管器官牵连较少。
几乎全部患者显示的Borg标度都低了两分以上；没有血液去饱和作用变化的记录。
察觉心血管器官牵连较少和发觉疲劳的主观感觉减弱两者意想不到地证明了小剂量的肌酸给药大大提高了肌肉的能量代谢效率。从临床观点看，这一结果无疑具有相当的重要性，给心脏和/或呼吸功能不全患者服用小剂量的肌酸，能使他们获得较大的运动自主性，提高独立性和改善生活质量。
Claims (3)
1.肌酸在制备治疗心脏和/或呼吸功能不全的药物方面的用途，其特征在于所述药物中肌酸的剂量为1-4g/日。
2.按照权利要求1的用途，其中所述药物用于治疗晚期阻塞性支气管病。
3.按照权利要求1或2的用途，其中所述药物为口服给药的形式。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT96MI002408A IT1298420B1 (it) | 1996-11-19 | 1996-11-19 | Uso della creatina nell'insufficienza cardio-respiratoria |
| ITMI96A002408 | 1996-11-19 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97199783A Division CN1237904A (zh) | 1996-11-19 | 1997-11-10 | 肌酸的新用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1623534A true CN1623534A (zh) | 2005-06-08 |
Family
ID=11375243
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA200410079798XA Pending CN1623534A (zh) | 1996-11-19 | 1997-11-10 | 肌酸的新用途 |
| CN97199783A Pending CN1237904A (zh) | 1996-11-19 | 1997-11-10 | 肌酸的新用途 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97199783A Pending CN1237904A (zh) | 1996-11-19 | 1997-11-10 | 肌酸的新用途 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6242490B1 (zh) |
| EP (1) | EP0941081B1 (zh) |
| CN (2) | CN1623534A (zh) |
| AR (1) | AR009425A1 (zh) |
| AT (1) | ATE230983T1 (zh) |
| BR (1) | BR9713514A (zh) |
| DE (1) | DE69718506T2 (zh) |
| DK (1) | DK0941081T3 (zh) |
| ES (1) | ES2191206T3 (zh) |
| IT (1) | IT1298420B1 (zh) |
| PT (1) | PT941081E (zh) |
| RU (1) | RU2202345C2 (zh) |
| WO (1) | WO1998022099A2 (zh) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3384539B2 (ja) * | 1997-09-05 | 2003-03-10 | 義之 内田 | 喘息治療剤 |
| EP1051914A1 (de) * | 1999-05-08 | 2000-11-15 | DSM Fine Chemicals Austria GmbH | Verwendung von Kreatin als Futterzusatz |
| US20030212130A1 (en) * | 2000-09-14 | 2003-11-13 | Miller Donald W. | Creatine ester anti-inflammatory compounds and formulations |
| US9833427B2 (en) * | 2000-09-14 | 2017-12-05 | Board Of Regents Of The University Of Nebraska | Creatine ester anti-inflammatory compounds and formulations |
| US20030212136A1 (en) | 2001-09-14 | 2003-11-13 | Vennerstrom Jonathan L. | Creatine ester pronutrient compounds and formulations |
| US20040013732A1 (en) * | 2001-09-25 | 2004-01-22 | Michael Farber | Starch-based delivery system for creatine |
| US20080160086A1 (en) * | 2004-02-19 | 2008-07-03 | Scepter Holdings, Inc. | Delivery Systems For Calcium |
| US20060025475A1 (en) * | 2004-07-29 | 2006-02-02 | Stanley Antosh | Use of methyl pyruvate for the purpose of increasing muscle energy production. |
| US20060052448A1 (en) * | 2004-09-04 | 2006-03-09 | Mr. Stanley Antosh | Use of methyl pyruvate or methyl pyruvic acid for the treatment of diseases of the nervous system and for protecting a human central nervous system against neuronal degeneration caused by defective intracellular energy production. |
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|---|---|---|---|---|
| FR2244534B1 (zh) * | 1973-06-27 | 1977-07-01 | Biotherax Lab | |
| US4783530A (en) * | 1986-11-13 | 1988-11-08 | Marion Laboratories, Inc. | 8-arylxanthines |
| US5470838A (en) * | 1987-10-28 | 1995-11-28 | Pro-Neuron, Inc. | Method of delivering exogenous uridine or cytidine using acylated uridine or cytidine |
| GB9215746D0 (en) * | 1992-07-24 | 1992-09-09 | Hultman Eric | A method of increasing creatine supply depot |
| AU3086897A (en) * | 1996-06-28 | 1998-01-21 | Ipr-Institute For Pharmaceutical Research Ag | Drug preparations, containing creatine with at least one salt of calcium, magnesium, manganese or zinc |
-
1996
- 1996-11-19 IT IT96MI002408A patent/IT1298420B1/it active IP Right Grant
-
1997
- 1997-11-10 BR BR9713514-3A patent/BR9713514A/pt unknown
- 1997-11-10 WO PCT/EP1997/006225 patent/WO1998022099A2/en not_active Ceased
- 1997-11-10 CN CNA200410079798XA patent/CN1623534A/zh active Pending
- 1997-11-10 RU RU99112945/14A patent/RU2202345C2/ru not_active IP Right Cessation
- 1997-11-10 CN CN97199783A patent/CN1237904A/zh active Pending
- 1997-11-10 DK DK97951157T patent/DK0941081T3/da active
- 1997-11-10 AT AT97951157T patent/ATE230983T1/de not_active IP Right Cessation
- 1997-11-10 DE DE69718506T patent/DE69718506T2/de not_active Expired - Fee Related
- 1997-11-10 EP EP97951157A patent/EP0941081B1/en not_active Revoked
- 1997-11-10 PT PT97951157T patent/PT941081E/pt unknown
- 1997-11-10 US US09/284,465 patent/US6242490B1/en not_active Expired - Fee Related
- 1997-11-10 ES ES97951157T patent/ES2191206T3/es not_active Expired - Lifetime
- 1997-11-13 AR ARP970105291A patent/AR009425A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US6242490B1 (en) | 2001-06-05 |
| EP0941081A2 (en) | 1999-09-15 |
| ITMI962408A1 (it) | 1998-05-19 |
| DE69718506D1 (de) | 2003-02-20 |
| ITMI962408A0 (it) | 1996-11-19 |
| WO1998022099A3 (en) | 1998-07-09 |
| RU2202345C2 (ru) | 2003-04-20 |
| ES2191206T3 (es) | 2003-09-01 |
| BR9713514A (pt) | 2000-02-29 |
| PT941081E (pt) | 2003-04-30 |
| DE69718506T2 (de) | 2003-07-31 |
| WO1998022099A2 (en) | 1998-05-28 |
| IT1298420B1 (it) | 2000-01-05 |
| DK0941081T3 (da) | 2003-04-22 |
| AR009425A1 (es) | 2000-04-12 |
| ATE230983T1 (de) | 2003-02-15 |
| CN1237904A (zh) | 1999-12-08 |
| EP0941081B1 (en) | 2003-01-15 |
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